87 Perinatal hemochromatosis (PH) is a rare neonatal liver disease of unknown cause(s), usually presenting as liver failure within the first weeks of life. Clinical features of chronic liver injury are consistent with liver injury beginning in utero. PH is often fatal or requires neonatal liver transplantation; spontaneous survivors may have only trivial chronic liver disease. Medical treatment with an "anti-oxidant cocktail" has been advocated. The aim of this work was to develop a prospective fetal surveillance programme for subsequent pregnancies in families where one infant had had PH, complemented by rapid diagnosis and institution of treatment, if appropriate. We report our initial experience with this strategy in two consecutive infants. Strategy:Fetal surveillance: MR scans were obtained at ∼28, 32, 36 wks gestation or until fetal hepatic iron overload was detected. MR findings in the normal neonate were used as reference for fetal studies. Neonatal diagnosis: The at-risk newborn was assessed as soon as possible. Liver function tests, serum ferritin, tests to exclude competing diagnoses, and MR scan were performed immediately; salivary gland (buccal) biopsy was reserved for uncertain cases; liver biopsy was not required. Neonatal treatment: Infants in whom PH was the most likely diagnosis were treated with the standard "antioxidant cocktail." Results: Infant 1 had only one MR study, negative at 34 wks gestation. She was spontaneously born at term, appeared well initially but showed hepatic insufficiency at 3 d. Treatment with the full "anti-oxidant cock-tail" was commenced and she stabilized over the next 2 mos and is well at 15 mos-old. Infant 2 had negative MR at 28 wks gestation, positive MR at 32 wks. She was born spontaneously at term, had coagulopathy and metabolic acidosis almost immediately. She was treated with "cocktail" minus PGE1 because of a PDA. She stabilized over the next 7 wks and is well at 14 mos-old. Liver biopsy performed when she was 12 mos-old was histologically normal. Conclusion: Fetal MR studies may not be informative; rapid diagnosis/institution of treatment appears critically important. Although initial experience with this prospective strategy is encouraging, further validation of the diagnostic and therapeutic interventions is required.